Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.

Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation.

The BEN domain protein LIN-14 coordinates neuromuscular positioning during epidermal maturation.

Development and function of an organism depend on coordinated inter-tissue interaction. How such interactions are maintained during tissue renewal and reorganization remains poorly understood. Here, we find that BEN domain transcription factor LIN-14 is required in epidermis for maintaining the position of motor neurons and muscles during developmental tissue reorganization.

Morphological change in an isolated population of red squirrels () in Britain.

The mechanical properties of dietary items are known to influence skull morphology, either through evolution or by phenotypic plasticity. Here, we investigated the impact of supplementary feeding of peanuts on the morphology of red squirrels () from five populations in Britain (North Scotland, Borders, Jersey and two temporally distinct populations from Formby (Merseyside)). Stable isotope analysis confirmed dietary ecology in 58 specimens.

Autoactive CNGC15 enhances root endosymbiosis in legume and wheat.

Nutrient acquisition is crucial for sustaining life. Plants develop beneficial intracellular partnerships with arbuscular mycorrhiza (AM) and nitrogen-fixing bacteria to surmount the scarcity of soil nutrients and tap into atmospheric dinitrogen, respectively. Initiation of these root endosymbioses requires symbiont-induced oscillations in nuclear calcium (Ca) concentrations in root cells.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

β3 accelerates microtubule plus end maturation through a divergent lateral interface.

β-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents.

Stepwise order in protein complex assembly: approaches and emerging themes.

Protein-based nanomachines drive every cellular process. An explosion of high-resolution structures of multiprotein complexes has improved our understanding of what these machines look like and how they work, but we still know relatively little about how they assemble in living cells. For example, it has only recently been appreciated that many complexes assemble co-translationally, with at least one subunit still undergoing active translation while already interacting with other subunits.

The potential for glacial flour to impact soil fertility, crop yield and nutrition in mountain regions.

Novel sustainable agricultural strategies that enhance soil nutrients and human nutrition are crucial for meeting global food production needs. Here, we evaluate the potential of "glacial flour," a naturally crushed rock produced by glaciers known to be rich in nutrients (P, K, and micronutrients) needed for plant growth. Our proof-of-concept study, investigated soybean ( var.

Canonical Wnt signalling from the area opaca induces and maintains the marginal zone in pre-primitive-streak stage chick embryos.

In chick embryos before primitive streak formation, the outermost extra-embryonic region, known as the area opaca (AO), was generally thought to act only by providing nutrients and mechanical support to the embryo. Immediately internal to the AO is a ring of epiblast called the marginal zone (MZ), separating the former from the inner area pellucida (AP) epiblast. The MZ does not contribute cells to any part of the embryo but is involved in determining the position of primitive streak formation from the adjacent AP epiblast.

CD44 and Ezrin restrict EGF receptor mobility to generate a novel spatial arrangement of cytoskeletal signaling modules driving bleb-based migration.

Cells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastatic melanoma cells migrating in non-adhesive confinement. Using high-resolution time-lapse imaging and specific molecular perturbations, we found that EGF signaling via PI3K stabilizes and maintains a polarized leader bleb.

Reducing Cofilin dosage makes embryos resilient to heat stress.

In addition to regulating the actin cytoskeleton, Cofilin also senses and responds to environmental stress. Cofilin can promote cell survival or death depending on context. Yet, many aspects of Cofilin's role in survival need clarification.

ENDOTHELIAL PROX1 INDUCES BLOOD-BRAIN BARRIER DISRUPTION IN THE CENTRAL NERVOUS SYSTEM.

The central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific overexpression mutants.

Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer.

Computerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules.

Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease.

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohn's disease (CD) model (Tnf), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host's immune susceptibility to drive region-specific disease. We identified an intracellular bacterium and murine counterpart to the human sexually transmitted , as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD.

Valosin-containing protein (VCP), a component of tumor-derived extracellular vesicles, impairs the barrier integrity of brain microvascular endothelial cells.

Metastases are the leading cause of cancer-related deaths, and their origin is not fully elucidated. Recently, studies have shown that extracellular vesicles (EVs), particularly small extracellular vesicles (sEV), can disrupt the homeostasis of organs, promoting the development of a secondary tumor. However, the role of sEV in brain endothelium and their association with metastasis related to breast cancer is unknown.

miR-449a/miR-340 reprogram cell identity and metabolism in fusion-negative rhabdomyosarcoma.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains in an undifferentiated state due to transcriptional and post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for the majority of diagnoses in the pediatric population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via post-transcriptional regulation of messenger RNAs (mRNAs).

E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.

Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

Molecular and cellular targets of GABAergic anesthetics in the mesopontine tegmentum that enable pain-free surgery.

The mesopontine tegmental anesthesia area (MPTA) is a focal brainstem locus which, when exposed to GABAergic agents, induces brain-state transitioning from wakefulness to unconsciousness. Correspondingly, MPTA lesions render animals relatively insensitive to GABAergic anesthetics delivered systemically. Using chemogenetics, we recently identified a neuronal subpopulation within the MPTA whose excitation induces this same pro-anesthetic effect.

Transcription factor networks in cellular quiescence.

Many of the cells in mammalian tissues are in a reversible quiescent state; they are not dividing, but retain the ability to proliferate in response to extracellular signals. Quiescence relies on the activities of transcription factors (TFs) that orchestrate the repression of genes that promote proliferation and establish a quiescence-specific gene expression program. Here we discuss how the coordinated activities of TFs in different quiescent stem cells and differentiated cells maintain reversible cell cycle arrest and establish cell-protective signalling pathways.

Superstable lipid vacuoles endow cartilage with its shape and biomechanics.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis.

The people behind the papers - Stephen DiNardo and Gabriela Vida.

Stem cells exist within a niche, a microenvironment that regulates their activity, but the mechanisms by which niche cells influence stem cell behaviour are poorly understood. In this issue, Stephen DiNardo and colleagues reveal that the shape of the adult Drosophila testes niche, which is dependent on the cytoskeleton of the niche cells, is crucial to maintaining germinal stem cell function. To learn more about this work, we spoke to first author Gabriela Vida and corresponding author Stephen DiNardo, Professor of Cell and Developmental Biology at the University of Pennsylvania, USA.

Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KRAS oncogene-expressing tumor cells.

Proto-oncogene KRAS, GTPase (KRAS) is one of the most intensively studied oncogenes in cancer research. Although several mouse models allow for regulated expression of mutant KRAS, selective isolation and analysis of transforming or tumor cells that produce the KRAS oncogene remains a challenge. In our study, we present a knock-in model of oncogenic variant KRAS that enables the "activation" of KRAS expression together with production of red fluorescent protein tdTomato.

α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.

Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.